WO 2009/148121 (Patent Document 1) and Biomaterials, 2009, Vol. 30, p. 5156-5160 (Non-Patent Document 1) disclose that an amphiphilic block polymer having a polylactic acid chain as a hydrophobic block and a polysarcosine chain as a hydrophilic block self-assembles in an aqueous solution to form a polymeric micelle (lactosome) having a particle size of 30 nm or more. It is known that the lactosomes exhibit high retentivity in blood and the amount of the lactosomes accumulated in the liver is significantly reduced as compared to polymeric micelles that have been already developed. The lactosomes utilize the property that nanoparticles with a particle size of several tens of nanometers to several hundreds of nanometers retained in blood are likely to be accumulated in cancer (Enhanced Permeation and Retention (EPR) effect), and therefore can be used as nano-carriers for cancer site-targeting molecular imaging or drug delivery.
Journal of Controlled Release, Volume 161, Issue 3, 10 Aug. 2012, Pages 821-825 (Non-Patent Document 2) discloses three kinds of lactosomes prepared by, respectively, encapsulating three kinds of ICG (indocyanine green)-labeled polylactic acids different in stereochemistry (ICG-PLLA, ICG-PDLA, ICG-PDLLA) in the polymeric micelle (lactosome) composed of a linear type amphiphilic block polymer having a poly-L-lactic acid (PLLA) chain as an above-mentioned hydrophobic block and a polysarcosine chain as an above-mentioned hydrophilic block, and also discloses the influence of the stereochemistry of the ICG-labeled polylactic acid on the behavior of the lactosome in vivo. These lactosomes have a particle diameter of 35 nm or more.
A phenomenon, namely “Accelerated Blood Clearance (ABC) phenomenon” is known, in which an immune system is activated by administering polymeric micelles composed of a synthetic polymer to a living body once so that when the same polymeric micelles are administered again, they are accumulated in the liver due to the action of the immune system. Details of the mechanism of development of this ABC phenomenon are more or less clarified. YAKUGAKU ZASSHI, 2009, Vol. 129, No. 12, p. 1445-1451 (Non-Patent Document 3) reports that the development of the ABC phenomenon is suppressed when polymeric micelles having a particle size of 30 nm or less are used.